CDC recently received reports of three cases of Pneumocystis
carinii pneumonia among patients with hemophilia A and without
other
underlying disease. Two have died; one remains critically ill.
All
three were heterosexual males; none had a history of intravenous
(IV)
drug abuse. All had lymphopenia, and the two patients who were
specifically tested have had in vitro laboratory evidence of
cellular
immune deficiency. The case reports follow.

Patient 1: A 62-year-old resident of Westchester County, New
York, with a history of chronic hepatitis had received frequent
injections of Factor VIII concentrate for severe hemophilia for
many
years. In February 1981, he began to experience weight loss and
vague
right upper quadrant abdominal discomfort associated with
laboratory
evidence of increasing hepatic dysfunction. In December 1981,
while
hospitalized in Miami, Florida, for elective knee surgery, he
complained of cough and fever. He was lymphopenic, and chest
X-ray
revealed interstitial infiltrates compatible with viral pneumonia.
He
was discharged in late December after a brief course of
corticosteroids associated with overall clinical improvement. He
returned in severe respiratory distress a few days later. Open
lung
biopsy on January 5 revealed P. carinii, for which he received
sulfamethoxazole/trimethoprim (SMZ/TMP) during the 2 weeks before
death. P. carinii pneumonia and micronodular cirrhosis were
documented at post-mortem examination.

Patient 2: A 59-year-old lifelong resident of Denver,
Colorado,
noted the onset of gradual weight loss, dysphagia associated with
pharyngitis, aphthous-like ulcers, and anterior cervical adenopathy
beginning in October 1980. As a patient with severe hemophilia, he
had received frequent injections of Factor VIII concentrate for
several years. Weight loss continued over a period of months.
Oropharyngeal candidiasis was diagnosed in February 1982. He was
hospitalized in May 1982 with symptoms including nausea, vomiting,
and
recurrent fever. Pneumonia was diagnosed, and P. carinii and
cytomegalovirus (CMV) were repeatedly identified from lung tissue
or
bronchial secretions using histopathologic and culture techniques.
Therapy with SMZ/TMP and pentamidine isethionate continued until
death
on July 5, 1982. Laboratory evidence for cellular immune
dysfunction
included absent mitogen responses and depletion of the T-helper
lymphocyte cell population, relative increase in T-suppressor
cells,
and resultant inverted T-helper/T-suppressor ratio.

Patient 3: A previously healthy 27-year-old lifelong resident
of
northeastern Ohio developed fever, urinary frequency and urgency,
and
extreme lassitude in July 1981. He had frequently received
parenteral
Factor VIII concentrate for severe hemophilia. Bilateral pneumonia
was diagnosed in October 1981, and open lung biopsy revealed P.
carinii. He responded successfully to a 3-week course of SMZ/TMP.
In
February 1982, he received ketoconazole to suppress repeated
episodes
of oral candidiasis. He was hospitalized again in April with
fever,
splenomegaly, anemia, and lymphopenia. An extensive tumor work-up
(including laparotomy) did not uncover an underlying malignancy.
Cultures of bone marrow, liver, mesenteric lymph nodes, and blood
grew
Mycobacterium avium. In vitro immunological testing in March
indicated a reduction in absolute number of circulating T-cells.
Subsequent, more extensive testing documented the lack of
lymphocyte
responsiveness to mitogens, absolute and relative decrease in
T-helper
cells, relative increase in T-suppressor cells, and resultant
inverted
T-helper/T-suppressor ratio.

Editorial Note

Editorial Note: Pneumocystis carinii pneumonia has not been
previously reported among hemophilia patients who have had no other
underlying diseases and have not had therapy commonly associated
with
immunosuppression. A review of the Parasitic Disease Drug
Service's
records of requests for pentamidine isethionate for 1980-1982
failed
to identify hemophilia among the underlying disorders of patients
for
whom pentamidine was requested for Pneumocystis carinii therapy.

The clinical and immunologic features these three patients
share
are strikingly similar to those recently observed among certain
individuals from the following groups: homosexual males,
heterosexuals
who abuse IV drugs, and Haitians who recently entered the United
States.(1-3) Although the cause of the severe immune dysfunction
is
unknown, the occurrence among the three hemophiliac cases suggests
the
possible transmission of an agent through blood products.

Hemophilia A is a sex-linked, inherited disorder characterized
by
a deficiency in Factor VIII activity. There are an estimated
20,000
patients with hemophilia A in the United States (4). Severity of
disease is classified according to percentage of endogenous Factor
VIII activity. Approximately 60% of the 20,000 are classified as
severe, and 40% are classified as moderate (4). Factor VIII
deficiency can be treated with intravenous administration of
exogenous
Factor VIII as either cryoprecipitate made from individual units of
fresh frozen plasma or lyophilized Factor VIII concentrate
manufactured from plasma pools collected from as many as a thousand
or
more donors.

CDC has notified directors of hemophilia centers about these
cases
and, with the National Hemophilia Foundation, has initiated
collaborative surveillance. A Public Health Service advisory
committee is being formed to consider the implication of these
findings. Physicians diagnosing opportunistic infections in
hemophilia patients who have not received antecedent
immunosuppressive
therapy are encouraged to report them to the CDC through local and
state health departments.

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